Approximately 350,000 cardiac arrests occur each year in the United States. Up to half of these patients can be resuscitated successfully. In the past only 10% to 30% of comatose post-cardiac arrest patients had a good neurologic recovery, but these numbers will likely improve with the increasing use of therapeutic hypothermia. Early accurate prediction of neurologic outcome in comatose post-cardiac arrest patients is an important healthcare issue. Currently available prognostic variables are limited in that they identify only about one-third of poor outcome patients reliably, they do not accurately assess long-term outcome in survivors, and they have not been validated in patients undergoing therapeutic hypothermia. As a consequence, in current clinical practice, many comatose post-cardiac arrest patients are taken off life support early, based on an assumption of a poor prognosis, despite the absence of prognosticators that are highly specific for poor outcome. The overall goal of this research is to determine the value of state-of-the art MRI, quantitative diffusion-weighted imaging MRI (DWI), in conjunction with serum biomarkers for cerebral injury in predicting neurologic outcome of comatose post-cardiac arrest patients during the first few days after the arrest. In this 4-year study, 110 consecutive comatose post-cardiac arrest patients will undergo MRI between 36 and 96 hours after the arrest and serum biomarkers (S100b protein and neuron specific enolase) will be measured at 24, 48, and 72 hours. The treating team will be blinded to the DWI and biomarker results. Functional outcome at 6 months will be determined by an independent and blinded adjudication panel. Tissue fate will be determined by pathology specimens in those who die, and by chronic phase MRI in survivors. In our primary analysis we will determine whether DWI in conjunction with serum markers can reliably identify a larger proportion of patients with a poor outcome than conventional methods (neurologic exam and neurophysiologic tests). We will also determine the prognostic value of DWI and biomarkers alone in predicting outcome at 6 months. Finally, we will determine the relationships between DWI and tissue fate. The results of this study may substantially improve the accuracy of outcome prediction in comatose post- cardiac arrest patients in the future and hence safe lives as well as resources. Further, they may lead to the development of practice guidelines for the use of MRI and serum markers in these patients. PUBLIC HEALTH RELEVANCE: Patients who suffer a heart attack may present to the hospital in a comatose state as a result of transient interruption of blood flow to the brain. During the first few days of the hospitalization the physicians are oftentimes uncertain whether the patient is able to awaken, or whether he or she has sustained irreversible brain injury, leaving him/her permanently in a coma. Information obtained from the neurological examination is usually limited in predicting the patient's long term outcome. In this study we propose to assess the value of state-of-the art brain imaging techniques (MRI), and blood tests in predicting outcome in these patients. The results of this study may substantially improve early outcome prediction in comatose heart attack patients in the future, and hence save lives as well as health care resources.